Diseases of bacterial origin are often associated with high morbidity and mortality. We have recently demonstrated that the fever accompanying a bacterial infection in reptiles leads to a reduction in mortality (Kluger et al., 1975; Bernheim and Kluger, 1976b). A comparison of the febrile responses of reptiles with birds and mammals demonstrates striking similarities and suggests a common evolutionary origin of the febrile mechanism in birds and mammals from some primitive reptile (D'Alecy and Kluger, 1975). If a common origin exists for the febrile mechanism then it is likely that the function of fever is also similar; that is, fever evolved as a mechanism to enhance the host defenses against pathogenic micro-organisms. Therefore, the research outlined in this proposal is designed to: 1. Test the hypothesis that the fever observed during bacterial infections in birds and mammals is of adaptive value to the host. 2. Test methods which can be used to generate an elevation in body temperature in populations of animals as a possible form of fever therapy (providing the fever observed in bacterially-infected birds and mammals is beneficial.) 3. Extend our comparative investigations on the characteristics of reptilian fever. 4. Attempt to determine the mechanism(s) behind the beneficial value of fever in reptiles. 5. Further characterize the febrile responses of amphibians and test the hypothesis that the fever observed in amphibians has survival value.